In recent years, a need has arisen for the manufacture of pharmaceutical powder dispersions of micron and sub-micron particle size having a controlled, narrow particle size distribution. Applications for such powders include, for example, pharmaceutical aerosol delivery by dry powder inhalers, increasing bioavailability of water insoluble drugs and haemostatic devices composed of a biodegradable composite matrix into which lyophilized powders of clotting factors are impregnated. The process of milling a powder to micron and sub-micron particle size is known as micronization.
Among the known micronization methods are methods which involve high shear rates and high energy inputs, such as jet milling or pulverizing systems, ball milling, high-pressure homogenization and microfluidization. Such methods are generally incompatible with biological molecules which are sensitive to thermal and/or physical degradation. Other, gentler, known methods include spray drying, recrystallization, emulsion-solvent extraction and methods using supercritical fluids such as Rapid Expansion of Supercritical Solutions (RESS).
Whirl or vortex chambers for milling are also known. For example, U.S. Pat. No. 4,502,641 discloses a combination of the jet milling principle with a vortex chamber. There are also known milling vortex chambers which perform a so-called resonance whirl milling. WO 94/08719 describes a whirl chamber milling apparatus fitted with tangential fluid injection nozzles which performs a so-called “resonance vortex grinding”.
U.S. Pat. No. 5,855,326 to Beliaysky, whose entire contents are incorporated by reference, discloses a whirl milling chamber for fine comminution of a particulate solid material, the chamber being formed in a housing having a substantially cylindrical shape with two end faces and a side wall provided with one or more tangential nozzles for the injection of a working fluid into the chamber and creating a vortex therein, said chamber comprising means for the introduction there into a particulate solid material to be comminuted, an axially disposed discharge passage provided in one or both said end faces, and control means in the form of one or more mechanical elements adapted to interact, when the vortex is created, with its layers moving close to inner walls of the chamber, thereby enabling for control of the comminution. Operation of the whirl chamber is exemplified in the patent using sand.
U.S. Pat. No. 6,789,756 to Beliaysky, whose entire contents are also incorporated by reference, discloses an improved vortex mill for milling a substantially particulate solid material, which includes one or more working chambers. The mill also includes one or more working fluid inlets and one or more discharge ports. One or more working fluid inlets together with one or more discharge ports facilitate the vortex flow within the one or more working chambers. There are also one or more feed inlets to provide milling of the solid material, which is discharged from one or more discharge ports. In addition, there is an apparatus for inducing controlled perturbations in the flow of the working fluid in the one or more working chambers, thereby to improve the milling of the solid material in the vortex flow.
The Hercules fibrin fleece is a haemostatic device composed of a biodegradable composite matrix of non woven Vicryl™ knitted into woven Oxidized Regenerated Cellulose (ORC, Interceed™), into which lyophilized powders of fibrinogen and thrombin are impregnated via a suspension in a volatile solvent.